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2-200613804-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001159.4(AOX1):c.1449G>A(p.Arg483=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,610,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

AOX1
NM_001159.4 splice_region, synonymous

Scores

2
Splicing: ADA: 0.02001
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.91
Variant links:
Genes affected
AOX1 (HGNC:553): (aldehyde oxidase 1) Aldehyde oxidase produces hydrogen peroxide and, under certain conditions, can catalyze the formation of superoxide. Aldehyde oxidase is a candidate gene for amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-200613804-G-A is Benign according to our data. Variant chr2-200613804-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 737210.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.91 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AOX1NM_001159.4 linkuse as main transcriptc.1449G>A p.Arg483= splice_region_variant, synonymous_variant 15/35 ENST00000374700.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AOX1ENST00000374700.7 linkuse as main transcriptc.1449G>A p.Arg483= splice_region_variant, synonymous_variant 15/351 NM_001159.4 P1
AOX1ENST00000485106.5 linkuse as main transcriptn.358G>A splice_region_variant, non_coding_transcript_exon_variant 3/221
AOX1ENST00000465297.5 linkuse as main transcriptn.381G>A splice_region_variant, non_coding_transcript_exon_variant 3/232
AOX1ENST00000485965.5 linkuse as main transcriptn.502G>A splice_region_variant, non_coding_transcript_exon_variant 4/44

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00144
AC:
219
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00497
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000378
AC:
94
AN:
248980
Hom.:
0
AF XY:
0.000275
AC XY:
37
AN XY:
134476
show subpopulations
Gnomad AFR exome
AF:
0.00481
Gnomad AMR exome
AF:
0.000438
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000151
AC:
220
AN:
1458630
Hom.:
0
Cov.:
30
AF XY:
0.000135
AC XY:
98
AN XY:
725532
show subpopulations
Gnomad4 AFR exome
AF:
0.00459
Gnomad4 AMR exome
AF:
0.000562
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000648
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00145
AC:
220
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.00146
AC XY:
109
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.00498
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000227
Hom.:
0
Bravo
AF:
0.00165
Asia WGS
AF:
0.00144
AC:
5
AN:
3476

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 19, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
6.5
Dann
Benign
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.020
dbscSNV1_RF
Benign
0.26
SpliceAI score (max)
0.19
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141842645; hg19: chr2-201478527; COSMIC: COSV65983428; API